Secretory Cell Outgrowth (SCOUT) in the Distal Fallopian Tube: A Clonal Expansion of Secretory Cells Linked to Cancer Risk?
E Chen, M Mehrad, KK Mehra, CP Crum. Brigham and Women's Hospital, Boston, MA
Background: Alterations in the fallopian tube mucosa have been described in association with ovarian cancer and more recently, secretory cell outgrowth (SCOUT) has been described in association with p53 mutations, and termed the "p53 signature". On the premise that p53 signatures are just one component of clonal expansion in the tube, we examined the relative frequency of p53-negative SCOUTs in the distal fallopian tubes from women with and without BRCA mutations and compared their frequency in these and women with pelvic serous carcinoma of tubal and ovarian origin.
Design: Normal appearing fallopian tubes from women with and without genetic risk (BRCA+) for pelvic serous cancer (PSC) and women with and without PSC were immunostained for secretory (bcl-2, pax-8) and ciliated (p73) epithelial cell phenotype. Selected cases were stained with H2AX (for evidence of DNA damage/repair). Secretory cell outgrowth (SCOUT) defined as 20 or more consecutive secretory cells without intervening ciliated cells, were scored, characterized by appearance and their frequency compared between the aforementioned groups by chi square analysis.
Results: SCOUTs were identified in both high (BRCA+) and low-risk women at equal frequency and in both proximal and distal tubal mucosa, at approximately 2.5 per 100x field of mucosa examined. SCOUTs consisted of either strongly bcl-2 positive pseudo-stratified or negative to weakly bcl-2 positive cuboidal epithelia. In all cases, p73 staining was negative, consistent with a secretory phenotype. SCOUTs displayed a greater trend in frequency in tubes from patients with presumed tubal carcinoma relative to other ovarian carcinomas (3.4 vs 1.3, p = 0.12). SCOUTs were typically H2AX negative.
Conclusions: SCOUTs are common in both proximal and distal fallopian tubes and fulfill histologic and histochemical criteria for a clonal expansion of secretory type cells, including positive staining for bcl-2 and pax-8, negative staining for p73 and an absence of intervening ciliated epithelium. The absence of H2AX staining suggests that this cellular expansion may result from milder genomic disturbances than the typical p53 signature. The concept of multiple clones of SCOUT linked to genotoxic stress in the distal tube is remarkable simlar to some pathways in the endometrium and merits further study as an additional intra or extra tubal pathway to pelvic epithelial malignancy.
Category: Gynecologic & Obstetrics
Tuesday, March 23, 2010 8:00 AM
Platform Session: Section D, Tuesday Morning